1. Field of the Invention
The present invention relates to a compound for promoting regeneration and differentiation of neural stem cells.
2. The Prior Arts
Neural stem cells (NSCs) are characterized as undifferentiated cells that have the capacity to self-renew and differentiate into other neural cells such as neurons, astrocytes and oligodendrocytes. NSCs can renew and differentiate in the presence of stimulating factors under in vitro cultural conditions. These differentiated cells play important roles during the development of central nervous system in mammals and also in the function of the fully developed nervous system in animals. NSCs can be isolated from the cortex of the brain of many mammals (such as mice, rats, pigs and humans) during their development before maturation. The NSCs in the central nervous system of humans are similar to those of rodents.
NSCs in mammals are present in mature organs as well as in the developing central nervous system. At the moment, one can also isolate neural stem cells from the embryonic brain of mammals; however, little is known on the mechanism of regulating endogenous neural stem cells.
The best method of treating a neurodegenerative disease is to restore and regenerate damaged or lost neural cells. Treatments in progress include replacing damaged cells through NSCs transplantation or activating endogenous NSCs in dormancy to “self-renew”.
Although scientists have some knowledge of using NSCs to restore damaged neural cells, they need to find a way to effectively control them as they grow and differentiate into function-defined cells. Previous reports indicate that NSCs could propagate in a medium supplemented with growth factors such as basic Fibroblast Growth Factor (bFGF), Epithelial Growth Factor (EGF), etc. It is also known that in the presence of these growth factors in a serum-free medium, NSCs grown in suspension have the propensity to aggregate and form so-called “neurospheres”. In addition, if these growth factors are removed and subsequently replaced with proper amount of known mitogenic factors, growth factors other than bFGF and EGF, or other neurotrophic factors, NSCs would most likely be stimulated into differentiation. The majority of the differentiated cells would be astrocytes (>90%), and only a few of them are neurons (<10%).
Many neurotrophic factors have been discovered in the past: Glial-derived Neurotrophic Factor (GDNF), Brain-derived Neurotrophic Factor (BDNF), Nerve Growth Factor (NGF), Neurotrophin-3 (NT3), Neurotrophin-4 (NT4), Platelet-derived Growth Factor (PDGF), and so on. Although these neurotrophic factors have been proven to promote the survival of neural cells, their clinical applications are limited. One reason is that their large molecular size prohibits them from passing the blood brain barrier (BBB).
If small molecular compounds could be found with the capability to activate endogenous NSCs, promote their growth and maintain their specificity, or even promote their differentiation into function able neurons, effective treatment or prevention of neurodegenerative diseases might become feasible. Through the effect of these compounds the success rate of NSCs transplantation into subjects may be improved.